1. Technical Field
The present invention relates to a process for the preparation of substituted 3′-hydrazino-biphenyl-3-carboxylic acid compounds. The present invention relates to a process for the preparation of 3′-{N′-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-pyrazol-4-ylidene]hydrazino}-2′-hydroxybiphenyl-3-carboxylic acid, its intermediate compounds and pharmaceutically acceptable salts thereof.
2. Description of the Related Art
Eltrombopag, also known as 3′-{N′-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-pyrazol-4-ylidene]-hydrazino}-2′-hydroxybiphenyl-3-carboxylic acid is represented by the structure of formula Ia.

Eltrombopag olamine, compound of formula II, is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Eltrombopag olamine is marketed under the brand name PROMACTA® in the United States (approved in November 2008) and under the brand name REVOLADE® in Europe (approved in March 2010).
Eltrombopag belongs to a class of substituted 3′-hydrazino-biphenyl-3-carboxylic acid compounds of formula I,

U.S. Pat. No. 7,160,870 (the '870 patent) discloses eltrombopag and its salts. U.S. Pat. No. 7,547,719 discloses eltrombopag olamine, bisethanolamine salt of eltrombopag. The '870 patent discloses a process for the preparation of eltrombopag as schematically represented by Scheme I.

The object of the present invention is to provide a novel method, which is more convenient and more efficient than the previously known method for the synthesis of substituted 3′-hydrazino-biphenyl-3-carboxylic acid compounds.